WELWYN GARDEN CITY, U.K.—
Heptares Therapeutics is a pioneer
in the discovery and
development of G protein-coupled receptors (GPCRs). Cubist
Pharmaceuticals Inc. has expertise in the development and commercialization of
products that address significant unmet medical needs in the acute
care and
hospital environment. Together, the two companies will collaborate on the
research and discovery of new medicines targeting GPCRs, membrane
proteins
involved in a broad range of biological processes and diseases.

The agreement gives
Cubist exclusive worldwide rights to
research, develop and commercialize products generated from the collaboration.
The collaborative research
agreement will focus on up to two GPCR drug targets
selected by Cubist. For the first target, Heptares will receive $5.5 million
upfront and up to
approximately $4 million in research funding, plus milestones
and royalties. Cubist also has the option to nominate a second GPCR target at a
later
point in the collaboration, which Heptares will work on according to
predetermined financials.

According to Malcolm Weir, Heptares' CEO, GPCRs play a
central role in many biological processes and are linked to a wide range of
disease
areas. GPCRs involved in CNS and metabolic diseases are perhaps the
best characterized, and there are a number of very attractive commercial
product
opportunities, "so it made sense for Heptares to focus its initial
efforts in this area to build its internal pipeline," says Weir.

The GPCR superfamily is the largest and single most
important family of drug targets in the human body. GPCRs are
expressed in
every type of cell in the body, where their function is to transmit signals
from outside the cell across the membrane to signaling
pathways within the cell,
between cells and between organ systems. More than 375 GPCRs are encoded in the
human genome, of which 225 have known ligands
and 150 are orphan targets. GPCRs
are the site of action of 25 to 30 percent of current drugs. Six of the top-10
and 60 of the top-200 best-selling
drugs in the United States in 2010 targeted
GPCRs. Seven of 37 drugs approved in 2012 by the U.S. Food & Drug
Administration target GPCRs.

Heptares is constantly talking to companies
about targets in
many indications.

"Cubist was one such company, a partner-of-choice and clear
business
leader in a space in which certain GPCRs could be medically very
important," Weir says. "Discussions moved forward very rapidly with a focus on
GPCRs
with significant medical promise in the acute care space."

Steve Gilman, Cubist's executive vice
president of research
and development and chief scientific officer, says, "Heptares is a recognized
leader in the GPCR field, and we are pleased to
collaborate in the pursuit of
potential new GPCR drug candidates. This partnership underscores our commitment
to develop a robust pipeline of novel
products that address high unmet medical
needs in patients with acute diseases. We bring expertise in the discovery,
development and commercialization
of therapies used in settings in and around
the hospital where acutely ill patients are treated for days or weeks—versus
the months or years of
treatment with a chronic care therapy."

He adds, "Cubist's acute-care channel strategy embraces
multiple therapeutic areas in the development and commercial areas of its
business, while our discovery and preclinical research remains focused on
antibiotics as well as non-opioid pain and inflammation."

An industry pioneer in GPCR structure-
based drug design
(SBDD), Heptares has built a special capability for discovering novel molecules
that target historically "undrugable" or
challenging GPCRs, according to Weir.
Heptares' integrated discovery platform includes proprietary technologies for
engineering stabilized GPCRs
(known as StaRs) in their natural pharmacological
conformations, identifying previously unknown chemistries for GPCR protein-drug
interactions and
deploying advanced fragment-based approaches to GPCR target
space for the first time.

The
company has generated structural and functional
information to drive SBDD for a range of important clinically validated GPCRs,
including Adenosine A2A,
Muscarinic M1, Orexin 1/2, MGluR5 and GLP-1. Heptares'
broad pipeline of novel product candidates against challenging GPCRs is designed
to transform
the treatment of serious diseases, including Alzheimer's disease,
Parkinson's disease, schizophrenia, depression, chronic insomnia, addiction,
migraine and diabetes, with the first two candidates expected to enter clinical
trials in 2013.

In the partnership, Heptares will focus on creating leads
using its SBDD platform (structure, chemistry and pharmacology) for Cubist to
take
into development. Cubist will be responsible for preclinical and clinical
development, as well as regulatory and commercial activities on a global basis.
The goal is to discover and develop new medicines that target the first (and
potentially a second) GPCR selected.

"The initial target is one that both companies believe is
well suited to addressing with Heptares' SBDD platform and also that a new
medicine hitting
this target will make a very important difference in the lives
of patients," Weir concludes.